(R)-flurbiprofen ethyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-flurbiprofen ethyl ester
• 英文别名: ethyl (2R)-2-(3-fluoro-4-phenylphenyl)propanoate
• 化学式: C₁₇H₁₇FO₂
• 分子量: 272.319
• InChiKey: JIYXQCWLSQSIJV-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  氟比洛芬 在 Candida antartica lipase B 作用下， 以 甲基叔丁基醚 、 苯 为溶剂， 反应 5.5h， 生成 (R)-flurbiprofen ethyl ester 、 (S)-N-flurbiprofenyl-1,2,4-triazole
  参考文献：
  名称：

  (R,S)-氟比洛芬基唑化物的脂肪酶催化醇解拆分用于制备(R)-NO-氟比洛芬酯前药

  摘要：

  摘要 为了制备 ( R )-flurbiprofenyl 酯、 ( S )-flurbiprofenyl zolide 和 ( S ) , 开发了脂肪酶催化的 ( R , S )-flurbiprofenyl azolide 在无水甲基叔丁基醚 (MTBE) 中的醇解反应。 -氟比洛芬。根据酶的对映选择性和活性，以( R , S )-氟比洛芬基4-溴吡唑啉和2,3-二溴-1-丙醇为底物制备南极假丝酵母脂肪酶B (CALB)的最佳反应条件为45 °C被选中，并导致出色的对映选择性（VR / VS = 200.3），与其他脂肪酶相比，快速反应对映异构体的比初始活性高两个数量级。热力学分析表明 -ΔΔ H 和 -ΔΔ S 对 -ΔΔ G = 14.03 kJ/mol 的贡献相等，因此具有出色的对映选择性，在最佳反应条件下。从彻底的动力学分析中估计的动力学常数成功地用于模拟两种对映异构体的时程转化

  DOI：

  10.1016/j.procbio.2011.01.017

文献信息

• METHOD FOR PRODUCING OPTICALLY ACTIVE 2-(2-FLUOROBIPHENYL-4-YL) PROPANOIC ACID
  申请人：TAISHO PHARMACEUTICAL CO., LTD.

  公开号：US20180282252A1

  公开（公告）日：2018-10-04

  A novel process for producing optically active 2-(2-fluorobiphenyl-4-yl)propanoic acid is disclosed. This production process is characterized in that a compound of formula [1] is reacted with magnesium and so forth to prepare an organometallic reagent, which is reacted with a compound of formula [2] in the presence of a catalytic amount of a nickel compound and a catalytic amount of an optically active compound of formula [3] to obtain a compound represented by formula [4] which is subsequently converted to a compound represented by formula [5] or a pharmaceutically acceptable salt thereof.

  揭示了一种生产光学活性2-(2-氟联苯基-4-基)丙酸的新工艺。该生产工艺的特点在于，化合物[1]与镁等反应，制备有机金属试剂，然后在存在催化量的镍化合物和光学活性化合物[3]的存在下，与化合物[2]发生反应，得到化合物[4]，随后将其转化为化合物[5]或其药用可接受的盐。
• [EN] PROCESS<br/>[FR] PROCÉDÉ
  申请人：AESICA PHARMACEUTICALS LTD

  公开号：WO2016110708A1

  公开（公告）日：2016-07-14

  There is described a process for the preparation of a stereospecific form of flurbiprofen, or a pharmaceutically acceptable salt thereof, which comprises subjecting a flurbiprofen ester, comprising a mixture (R)-(-)-flurbiprofen and (S)-(+)-flurbiprofen, to the action of an biocatalyst capable of stereo selective de-esterification of the ester; provided that the biocatalyst is not Aspergillus oryzae; Bacillus cereus C71; Candida Antarctica lipase B (Novozym ® 435); Candida cylindracea; Candida rugosa lipase; Carica papaya lipase; Pseudomonas sp. KCTC 10122BP and Serratia marcescens ES-2.

  本文描述了一种制备氟比洛芬立体异构体或其药学上可接受的盐的过程，包括将含有(R)-(-)-氟比洛芬和(S)-(+)-氟比洛芬混合物的氟比洛芬酯经过具有立体选择性脱酯酶能力的生物催化剂作用处理；但该生物催化剂不包括稻曲霉、谷氨酸杆菌C71、南极酵母脂肪酶B（Novozym®435）、圆筒假丝酵母、乳酸假丝酵母脂肪酶、木瓜脂肪酶、假单胞菌KCTC 10122BP和鲍氏杆菌ES-2。
• Biotransformation with whole microbial systems in a continuous flow reactor: resolution of (RS)-flurbiprofen using Aspergillus oryzae by direct esterification with ethanol in organic solvent
  作者：Lucia Tamborini、Diego Romano、Andrea Pinto、Martina Contente、Maria C. Iannuzzi、Paola Conti、Francesco Molinari

  DOI：10.1016/j.tetlet.2013.08.119

  日期：2013.11

  Cell-bound lipases of dry mycelium of Aspergillus oryzae were used in organic solvent for the resolution of racemic flurbiprofen by direct esterification with ethanol in a flow-chemistry reactor. Under flow conditions a significant reduction of the reaction time and an increase of the enantioselectivity were achieved compared to the batch mode. Moreover, the process was implemented by adding an in-line purification step integrated with the racemization of the unreacted flurbiprofen directly into a polymer-supported resin. (C) 2013 Elsevier Ltd. All rights reserved.
• Resolution of (R,S)-flurbiprofen catalysed by dry mycelia in organic solvent
  作者：Patrizia Spizzo、Alessandra Basso、Cynthia Ebert、Lucia Gardossi、Valerio Ferrario、Diego Romano、Francesco Molinari

  DOI：10.1016/j.tet.2007.08.051

  日期：2007.11

  Mycelia of Aspergillus oryzae display high enantioselectivity towards (R)-flurbiprofen and can be efficiently used in pure organic solvent for the resolution of (R,S)-flurbiprofen through esterification. The use of the lyophilized mycelia facilitates the separation process so that in one step the two enantiomers of flurbiprofen, which are both valuable for pharmaceutical applications, can be easily separated. The biotransformation can be carried out in different apolar solvents using different primary alcohols as nucleophiles under very mild conditions. (c) 2007 Elsevier Ltd. All rights reserved.